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Establishment of a Swiss Webster mouse model of pneumonic plague to meet essential data elements under the animal rule.

Abstract

A recombinant vaccine (rF1V) is being developed for protection against pneumonic plague. This study was performed to address essential data elements to establish a well-characterized Swiss Webster mouse model for licensing the rF1V vaccine using the FDA's Animal Rule. These elements include the documentation of challenge material characteristics, aerosol exposure parameters, details of the onset and severity of clinical signs, pathophysiological response to disease, and relevance to human disease. Prior to animal exposures, an evaluation of the aerosol system was performed to determine and understand the variability of the aerosol exposure system. Standardized procedures for the preparation of Yersinia pestis challenge material also were developed. The 50% lethal dose (LD(50)) was estimated to be 1,966 CFU using Probit analysis. Following the LD(50) determination, pathology was evaluated by exposing mice to a target LD(99) (42,890 CFU). Mice were euthanized at 12, 24, 36, 48, 60, and 72 h postexposure. At each time point, samples were collected for clinical pathology, detection of bacteria in blood and tissues, and pathology evaluations. A general increase in incidence and severity of microscopic findings was observed in the lung, lymph nodes, spleen, and liver from 36 to 72 h postchallenge. Similarly, the incidence and severity of pneumonia increased throughout the study; however, some mice died in the absence of pneumonia, suggesting that disease progression does not require the development of pneumonia. Disease pathology in the Swiss Webster mouse is similar to that observed in humans, demonstrating the utility of this pneumonic plague model that can be used by researchers investigating plague countermeasures.

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  • Authors

    Fellows P, Lin W, Detrisac C, Hu SC, Rajendran N, Gingras B, Holland L, Price J, Bolanowski M, House RV

    Source

    Clinical and vaccine immunology : CVI 19:4 2012 Apr pg 468-76

    MeSH

    Animal Structures
    Animals
    Disease Models, Animal
    Female
    Humans
    Lethal Dose 50
    Male
    Mice
    Plague
    Plague Vaccine
    Yersinia pestis

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    22336286